Biodistribution and radiation dosimetry of D-isomer of 4-borono-2-[F]fluoro-phenylalanine: A comparative PET/CT study with L-isomer in healthy human volunteers.

INTRODUCTION

L-isomer of 4-borono-2-F-fluoro-phenylalanine (L-[F]FBPA) was generally applied in clinic for boron neutron capture therapy (BNCT). With radiotracer validation, D-isomer of [F]FBPA (D-[F]FBPA) was found a higher tumor to normal brain tissue ratio (TBR) than its L-isomer on positron emission tomography (PET) in rat brain glioma. The present study was conducted as a first-in-human study to explore the biodistribution and radiation dosimetry of D-[F]FBPA in healthy human volunteers, compared with L-[F]FBPA.

METHODS

D-[F]FBPA or L-[F]FBPA was injected intravenously. Five whole-body PET scans were performed for each subject in the next 2 h. Organ time-activity curves were drawn by measuring SUV in volumes of interest. Absorbed dose coefficient of target organs and effective dose (ED) were estimated on OLINDA/EXM.

RESULTS

Two healthy volunteers (both males) and three healthy volunteers (2 males, 1 female) were intravenously injected with D-[F]FBPA (5.5-7.2 MBq/kg) and L-[F]FBPA (3.9-6.8 MBq/kg) respectively. Only limited accumulation of D-[F]FBPA was observed in healthy human brain, pancreas, liver, spleen and skeleton. The ED was calculated to be 0.026 mSv/MBq. Urinary bladder wall received the highest dose of 0.28 mGy/MBq, followed by kidneys (0.06 mGy/MBq), and all the other organs received less than 0.03 mGy/MBq. For L-[F]FBPA, higher uptake in brain, pancreas, liver, spleen and skeleton could be visualized, compared with D-[F]FBPA. The ED of L-[F]FBPA was 0.020 ± 0.001 mSv/MBq. Urinary bladder wall and kidneys still received the highest dose among organs but with lower values than those of D-[F]FBPA.

CONCLUSIONS

D-[F]FBPA had lower activity in normal brain, liver, spleen, pancreas and skeleton, compared with its L-isomer. D-[F]FBPA is safe from a radiological standpoint.

ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE

D-[F]FBPA was safe from a radiological standpoint, and had lower activity in normal brain, liver, spleen, pancreas and skeleton than its L-isomer. This study ensures the safety and validity of D-[F]FBPA for further clinical trials in patients with cancer.